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Funkční profilování komponentů komplexu transkripčních koaktivátorů SAGA v Arabidopsis
Sokolov, Rodion
Regulation of gene expression can be carried out by various mechanisms, one of them is enzyme-mediated modification of histones. Such enzymes often form large multi-subunit complexes to facilitate their enzymatic activity and substrate specificity. The Spt-Ada-Gcn5 acetyltransferase (SAGA) complex is a complex of transcriptional coactivators highly conserved between plants and yeast. In plants, SAGA can regulate gene expression through histone acetylation and deubiquitination. PHYTOCHROME-DEPENDENT LATE-FLOWERING (PHL)/SPT20 is a subunit of the structural module SAGA, that interacts with phytochrome B and thus regulates flowering, but at the same time its expression affects plant response to drought and nitrogen deficiency. In the experimental part of this work, the effect of PHL on resistance to other abiotic stresses, such as oxidative and osmotic stress was investigated. The response of plants defective in the gene encoding PHL to the given stresses was shown to be dependent on the photoperiod, whereby the impact of oxidative stress was more pronounced when grown under long-day conditions. On the contrary, plants were more sensitive to osmotic stress under short-day conditions. In this study, the metabolites present in the phl mutant line at a different concentration than in the standard plants were identified and may thus be responsible for the different response of this line to stress.
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Differences in histone acetylation in normoxia and hypoxia
Čepek, Pavel ; Poljaková, Jitka (advisor) ; Eckschlager, Tomáš (referee)
Histones and their N and C terminal tails undergo different covalent modifications that regulate gene transcription. Among these histone modifications are methylation, ubiquitinilation, SUMOylation, ADP- ribosylation, phosphorylation, proline izomerization, deimination and acetylation. Histone acetylation is regulated by histonacetyltransferases (HATs) and histondeacetylases (HDACs). The balance between acetylation/deacetylation influences chromatin condensation and thus regulates gene transcription. Acetylation balance is disrupted in many human cancers and this fact can contribute to the development of malignant diseases. Histondeacetylase inhibitors (HDACi) can restore this acetylation imbalance. One of these HDACi is valproic acid (VPA) which has been used in treatment of epilepsy for decades. VPA shows antitumour effect in many studies. Decreased expression of n-myc oncoprotein, inhibition of tumour growth and angiogenesis are one of these anticancer effects observed in neuroblastoma cell lines after treatment with VPA. Despite the fact that exact mechanism of antitumour effect of VPA remains unclear, one of the most important mechanisms is hyperacetylation of histone H3 and H4. It is shown in this work that VPA increases acetylation of histones H3 and H4 in human neuroblastoma cell lines...
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Epigenetické regulace u autoimunitních onemocnění se zaměřením na revmatoidní artritidu
Horková, Veronika ; Daňková, Pavlína (advisor) ; Hušáková, Markéta (referee)
Exact cause of rheumatoid arthritis, as well as other autoimmune diseases has not been identified yet. In last twenty years, epigenetics showed a new face of immune system. DNA methylation, modification of histones - proteins around which DNA is wrapped, or interference of small RNA sequences - microRNAs, these all are heritable changes outside the DNA sequence that provide another component involved in autoimmunity. Presented epigenetic mechanisms alter gene expression and thus facilitate production of pro- inflammatory factors leading to autoimmune reactions. Moreover, genes regulating apoptosis are also frequently targeted by epigenetic modifications. Not only these mechanisms provide another level of immune defense, they also explain higher female susceptibility to autoimmune diseases and the influence of environment on pathogenesis of these diseases.
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Histone modifications and methylation of polyomaviral genomes during the infection
Mrkáček, Michal ; Forstová, Jitka (advisor) ; Šmahelová, Jana (referee)
Similarly to other viruses, polyomaviruses require for their successful replication enzymes and other proteins encoded by their host cells. Additionally, because of their relatively small genome with only a few genes, polyomaviruses utilize for their efficient replication cellular regulation mechanisms. One of these regulations are posttranslational modifications of histones, which form nucleosomes together with viral DNA. The spectrum of these modifications is very wide, but in case of polyomaviruses, almost only ones studied are histone acetylations and methylations. Second possible regulation is a methylation of cytosine in CpG dinucleotides, which is associated with repression of gene expression. Current knowledge however suggest that polyomaviruses do not utilise this kind of modification. Moreover, because of a relatively small amount of CpG dinucleotides present in their genomes, they seem to avoid it. The goal of this work is to describe the individual types of these modifications and show their possible importance in the infectious cycle of polyomaviruses. Key words: polyomavirus, epigenetics, histone modification, DNA methylation, CpG dinucleotides
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Association of chromatin modifications with transgenerational abiotic stress memory of plants
Vyskočilová, Barbara ; Holá, Dana (advisor) ; Fischer, Lukáš (referee)
Plants are constantly exposed to various stressors which usually leads to changes in the expression of many different genes. This can be controlled at multiple levels, including modifications of chromatin structure. Some of these modifications may persist even after the period when the plant is exposed to stress and could possibly act as a kind of "stress memory". This work deals with so-called meiotic/transgeneration "stress memory" of plants caused by abiotic stressors. Compilation of studies dealing with this topic showed that they are still rather rare and usually originated from only a few laboratories. The majority of these studies was aimed only at the examination of DNA methylation and their design was not always optimal. In my opinion, true proofs of transgeneration "stress memory" of plants still remain to be presented; further, more properly designed studies are necessary. Powered by TCPDF (www.tcpdf.org)
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Histone modifications and methylation of polyomaviral genomes during the infection
Mrkáček, Michal ; Forstová, Jitka (advisor) ; Šmahelová, Jana (referee)
Similarly to other viruses, polyomaviruses require for their successful replication enzymes and other proteins encoded by their host cells. Additionally, because of their relatively small genome with only a few genes, polyomaviruses utilize for their efficient replication cellular regulation mechanisms. One of these regulations are posttranslational modifications of histones, which form nucleosomes together with viral DNA. The spectrum of these modifications is very wide, but in case of polyomaviruses, almost only ones studied are histone acetylations and methylations. Second possible regulation is a methylation of cytosine in CpG dinucleotides, which is associated with repression of gene expression. Current knowledge however suggest that polyomaviruses do not utilise this kind of modification. Moreover, because of a relatively small amount of CpG dinucleotides present in their genomes, they seem to avoid it. The goal of this work is to describe the individual types of these modifications and show their possible importance in the infectious cycle of polyomaviruses. Key words: polyomavirus, epigenetics, histone modification, DNA methylation, CpG dinucleotides
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Epigenetické regulace u autoimunitních onemocnění se zaměřením na revmatoidní artritidu
Horková, Veronika ; Daňková, Pavlína (advisor) ; Hušáková, Markéta (referee)
Exact cause of rheumatoid arthritis, as well as other autoimmune diseases has not been identified yet. In last twenty years, epigenetics showed a new face of immune system. DNA methylation, modification of histones - proteins around which DNA is wrapped, or interference of small RNA sequences - microRNAs, these all are heritable changes outside the DNA sequence that provide another component involved in autoimmunity. Presented epigenetic mechanisms alter gene expression and thus facilitate production of pro- inflammatory factors leading to autoimmune reactions. Moreover, genes regulating apoptosis are also frequently targeted by epigenetic modifications. Not only these mechanisms provide another level of immune defense, they also explain higher female susceptibility to autoimmune diseases and the influence of environment on pathogenesis of these diseases.
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Epigenetics mechanisms
Šornová, Veronika ; Černá, Marie (advisor) ; Koc, Michal (referee)
Epigenetics is the study of heritable changes in gene activities that are not caused by changes in the DNA sequence. Epigenetic mechanisms can be employed at many levels, from transcription to translation. They include DNA methylation, histone modification, and with it connected chromatin modification, and RNA interference. The result is the change of chromatin conformation leading to decrease or increase of certain gene expression, X-chromosome inactivation or gene imprinting. Epigenetic regulation plays important role in etiopatogenesis of multifactorial diseases. Genetic predisposing factors (in autoimmune diseases there are genes of major histocompatibility complex) and environmental factors, which affect our genome just through epigenetic modifications, are involved in their manifestation. Key words: Epigenetic mechanisms, DNA methylation, histone modification, RNA interference, genomic imprinting, X-chromosome inactivation, multifactorial disease.
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Differences in histone acetylation in normoxia and hypoxia
Čepek, Pavel ; Poljaková, Jitka (advisor) ; Eckschlager, Tomáš (referee)
Histones and their N and C terminal tails undergo different covalent modifications that regulate gene transcription. Among these histone modifications are methylation, ubiquitinilation, SUMOylation, ADP- ribosylation, phosphorylation, proline izomerization, deimination and acetylation. Histone acetylation is regulated by histonacetyltransferases (HATs) and histondeacetylases (HDACs). The balance between acetylation/deacetylation influences chromatin condensation and thus regulates gene transcription. Acetylation balance is disrupted in many human cancers and this fact can contribute to the development of malignant diseases. Histondeacetylase inhibitors (HDACi) can restore this acetylation imbalance. One of these HDACi is valproic acid (VPA) which has been used in treatment of epilepsy for decades. VPA shows antitumour effect in many studies. Decreased expression of n-myc oncoprotein, inhibition of tumour growth and angiogenesis are one of these anticancer effects observed in neuroblastoma cell lines after treatment with VPA. Despite the fact that exact mechanism of antitumour effect of VPA remains unclear, one of the most important mechanisms is hyperacetylation of histone H3 and H4. It is shown in this work that VPA increases acetylation of histones H3 and H4 in human neuroblastoma cell lines...
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